Microfluidic body-on-a-chip device and methods of use thereof

Abstract

A microfluidic device includes a base comprising a chamber configured to receive a microfluidic component. A sealing member includes a body, an inlet reservoir, and an outlet reservoir, where the inlet reservoir and the outlet reservoir communicate with the chamber through fluid passages when the sealing member and base are removably coupled. A microfluidic component removably within the chamber includes microfluidic channels on a surface thereof and a tissue culture chamber coupled to at least one of the microfluidic channels. The microfluidic channels and the tissue culture chamber are in fluid communication with the inlet and outlet reservoirs through the fluid passages to form a fluid circuit for directing fluid from the inlet reservoir, through the tissue culture chamber, to the outlet reservoir, and from the outlet reservoir back to the inlet reservoir upon tilting the microfluidic device to a forward tilted position and to a reverse tilted position, respectively.

What is claimed: 
     
       1. A microfluidic device comprising:
 a base comprising a base chamber; 
 a sealing member removably coupled to the base to provide a seal for the chamber, the sealing member comprising a body and a first inlet reservoir and a first outlet reservoir, wherein the first inlet reservoir and the first outlet reservoir are positioned within the body and communicating with the base chamber through a first set of fluid passages in the sealing member when the sealing member is coupled to the base; and 
 a first microfluidic component removably within the base chamber, the first microfluidic component comprising one or more microfluidic channels on a surface thereof and a first tissue culture chamber configured to house a first tissue culture coupled to at least one of the one or more microfluidic channels, wherein the one or more microfluidic channels comprise a first microfluidic channel in fluid communication with the first tissue culture chamber at a first end of the first tissue chamber, a second microfluidic channel in fluid communication with the first tissue culture chamber at a second end of the first tissue culture chamber opposite the first end, and a third microfluidic channel located separately on the first microfluidic component from the first microfluidic channel and the second microfluidic channel and not in fluid communication with the first tissue culture chamber, the first microfluidic channel, or the second microfluidic channel, wherein, when the first microfluidic component is within the base chamber, the one or more microfluidic channels and the first tissue culture chamber are positioned in fluid communication with the first inlet reservoir and the first outlet reservoir through the first set of fluid passages in the sealing member to form a first fluid circuit for directing a first flow of fluid from the first inlet reservoir, through the first tissue culture chamber, to the first outlet reservoir, and from the first outlet reservoir back to the first inlet reservoir upon tilting the microfluidic device to a forward tilted position and to a reverse tilted position, with respect to a horizontal axis, respectively, wherein the first flow of fluid to the first tissue chamber from the first fluid circuit is unidirectional when the microfluidic device is moving between the forward tilted and reverse tilted positions. 
 
     
     
       2. The microfluidic device as set forth in  claim 1 , wherein the first fluid circuit is configured to provide a first flow rate of the first flow of fluid to the first tissue culture chamber substantially similar to a first physiological flow rate in a first organ. 
     
     
       3. The microfluidic device as set forth in  claim 1 , wherein the one or more microfluidic channels have a width of about 5 μm to about 5 mm. 
     
     
       4. The microfluidic device as set forth in  claim 1 , wherein the first set of fluid passages comprise:
 a first capillary channel extending from the first inlet reservoir to the first microfluidic channel; 
 a second capillary channel extending from the second microfluidic channel to the first outlet reservoir to form the first fluid circuit from the first inlet reservoir, through the first tissue culture chamber, to the first outlet reservoir; 
 a third capillary channel extending from the first outlet reservoir to the third microfluidic channel; and 
 a fourth capillary channel extending from the third microfluidic channel to the first inlet reservoir to form a first backflow circuit between the first outlet reservoir and the first inlet reservoir. 
 
     
     
       5. The microfluidic device as set forth in  claim 1 , wherein the sealing member further comprises a threaded stem configured to mate with a corresponding threaded portion in the base to reversibly couple the sealing member to the base. 
     
     
       6. The microfluidic device as set forth in  claim 1 , wherein the sealing member further comprises a first alignment mechanism configured to align the one or more channels of the first microfluidic component with the first inlet reservoir and the first outlet reservoir. 
     
     
       7. The microfluidic device as set forth in  claim 1 , wherein the first microfluidic component further comprises a first porous membrane in the first tissue culture chamber to support tissue growth. 
     
     
       8. The microfluidic device as set forth in  claim 1  further comprising:
 a second microfluidic component removably within the base chamber in a stacked arrangement with the first microfluidic component, the second microfluidic component comprising another one or more microfluidic channels on a surface thereof and a second tissue culture chamber configured to house a second tissue culture coupled to at least one of the another one or more microfluidic channels. 
 
     
     
       9. The microfluidic device as set forth in  claim 8 , wherein the base chamber further comprises:
 a second inlet reservoir and a second outlet reservoir positioned within the body and communicating with the base chamber through a second set of fluid passages in the sealing member when the sealing member is coupled to the base, wherein, when the second microfluidic component is within the base chamber, the another one or more microfluidic channels and the second tissue culture chamber are positioned in fluid communication with the second inlet reservoir and the second outlet reservoir through the second set of fluid passages in the sealing member to form a second fluid circuit for directing a second flow of fluid from the second inlet reservoir, through the second tissue culture chamber, to the second outlet reservoir, and from the second outlet reservoir back to the second inlet reservoir upon tilting the microfluidic device to the forward tilted and to the reverse tilted position, with respect to the horizontal axis, respectively, wherein the second flow of fluid to the second tissue culture chamber from the second fluid circuit is unidirectional when the microfluidic device is moving between the forward tilted and reverse tilted positions. 
 
     
     
       10. The microfluidic device as set forth in  claim 9 , wherein the second fluid circuit is configured to provide a second flow rate of the second flow of fluid to the second tissue culture chamber substantially similar to a second physiological flow rate in a second organ. 
     
     
       11. The microfluidic device as set forth in  claim 9 , wherein the another one or more microfluidic channels further comprise:
 a fourth microfluidic channel in fluid communication with the second tissue culture chamber at a first end of the second tissue culture chamber; 
 a fifth microfluidic channel in fluid communication with the second tissue culture chamber at a second end of the second tissue culture chamber opposite the first end; 
 a sixth microfluidic channel positioned to receive the second flow of fluid from the second inlet reservoir and having a first hole in fluid communication with the fourth microfluidic channel of the second microfluidic component; 
 a seventh microfluidic channel having a second hole in fluid communication with the fifth microfluidic channel of the second microfluidic component; and 
 an eighth microfluidic channel positioned separately from sixth and seventh microfluidic channels and not in fluid communication with either the sixth or seventh microfluidic channels. 
 
     
     
       12. The microfluidic device as set forth in  claim 11 , wherein the second microfluidic component comprises a second alignment mechanism to align the first hole in the sixth microfluidic channel with sixth microfluidic channel and the second hole of the seventh microfluidic channel with the fifth microfluidic channel. 
     
     
       13. The microfluidic device as set forth in  claim 11 , wherein the second set of fluid passages comprise:
 a fifth capillary channel extending from the second inlet reservoir to the sixth microfluidic channel; 
 a sixth capillary channel extending from the seventh microfluidic channel to the second outlet reservoir to form the second fluid circuit from the second inlet reservoir, through the sixth microfluidic channel, through the first hole, through the fourth microfluidic channel, through the second tissue culture chamber, through the fifth microfluidic channel, through the second hole, through the seventh microfluidic channel, to the second outlet reservoir; 
 a seventh capillary channel extending from the second outlet reservoir to the eighth microfluidic channel; and 
 an eighth capillary channel extending from the eighth microfluidic channel to the second inlet reservoir to form a second backflow circuit between the second outlet reservoir and the second inlet reservoir. 
 
     
     
       14. The microfluidic device as set forth in  claim 1  further comprising:
 a first electrode located in the base and a second electrode located in the sealing member, wherein the first electrode and the second electrode are positioned to provide a current across the base chamber.